US20080306301A1 - Broad spectrum antimicrobial purification materials and methods for purifying fluids - Google Patents

Broad spectrum antimicrobial purification materials and methods for purifying fluids Download PDF

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Publication number
US20080306301A1
US20080306301A1 US12/171,267 US17126708A US2008306301A1 US 20080306301 A1 US20080306301 A1 US 20080306301A1 US 17126708 A US17126708 A US 17126708A US 2008306301 A1 US2008306301 A1 US 2008306301A1
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Prior art keywords
chlorhexidine
antimicrobial composition
substituted
dihydrate
alkynyl
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Abandoned
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US12/171,267
Inventor
Jan W. Gooch
Arthur W. Johnston
Arthur F. Johnston
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Watervisions International Inc
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Watervisions International Inc
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Publication date
Priority to US82043706P priority Critical
Priority to US11/539,422 priority patent/US7427409B2/en
Application filed by Watervisions International Inc filed Critical Watervisions International Inc
Priority to US12/171,267 priority patent/US20080306301A1/en
Publication of US20080306301A1 publication Critical patent/US20080306301A1/en
Abandoned legal-status Critical Current

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    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES, AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N47/00Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/40Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having a double or triple bond to nitrogen, e.g. cyanates, cyanamides
    • A01N47/42Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having a double or triple bond to nitrogen, e.g. cyanates, cyanamides containing —N=CX2 groups, e.g. isothiourea
    • A01N47/44Guanidine; Derivatives thereof
    • CCHEMISTRY; METALLURGY
    • C02TREATMENT OF WATER, WASTE WATER, SEWAGE, OR SLUDGE
    • C02FTREATMENT OF WATER, WASTE WATER, SEWAGE, OR SLUDGE
    • C02F1/00Treatment of water, waste water, or sewage
    • C02F1/50Treatment of water, waste water, or sewage by addition or application of a germicide or by oligodynamic treatment
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C275/00Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
    • C07C275/46Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups containing any of the groups, X being a hetero atom, Y being any atom, e.g. acylureas
    • C07C275/58Y being a hetero atom
    • C07C275/62Y being a nitrogen atom, e.g. biuret
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C279/00Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
    • C07C279/20Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups containing any of the groups, X being a hetero atom, Y being any atom, e.g. acylguanidines
    • C07C279/24Y being a hetero atom
    • C07C279/26X and Y being nitrogen atoms, i.e. biguanides
    • C07C279/265X and Y being nitrogen atoms, i.e. biguanides containing two or more biguanide groups

Abstract

An antimicrobial composition for use in water, air, and other fluid treatment applications is provided. The composition includes a biguanide dihydrate compound, such as a chlorhexidine dihydrate, which exhibits broad spectrum antimicrobial activity.

Description

    CROSS-REFERENCE TO RELATED APPLICATION
  • This is a continuation of U.S. application Ser. No. 11/539,422, filed Oct. 6, 2006, which claims the benefit of U.S. Provisional Application No. 60/820,437, filed Jul. 26, 2006. These applications are incorporated herein by reference in their entirety.
  • BACKGROUND OF THE INVENTION
  • This invention is generally in the field of antimicrobial materials useful in the purification of fluids, purification devices including antimicrobial materials, and methods of making and using such antimicrobial materials.
  • There is a general need for devices and methods to eliminate microorganisms from fluids for various applications, including the provision of safe or potable drinking water and breathable purified air. Many different methods are currently used for the purification of fluids. Representative examples include distillation, ion-exchange, chemical adsorption, filtering, and retention. Oftentimes, a number of different techniques must be combined to provide complete purification of fluids. These techniques can be costly, energy inefficient, and require significant technical expertise. Unfortunately, many low cost purification techniques do not adequately treat or remove harmful biological contaminants, bacteria, and viruses.
  • The Environmental Protection Agency (EPA) has set forth minimum standards for acceptance of a device proposed for use as a microbiological water filter. Common coliforms, represented by the bacteria E. coli and Klebsiella terrigena, must show a minimum 6-log reduction (99.9999% of organisms removed) from an influent concentration of 1×107 per 100 mL of water. Common viruses, represented by poliovirus 1 (LSc) and rotavirus (Wa or SA-11), which show a resistance to many treatment processes, must show a minimum 4-log reduction (99.99% of organisms removed), from an influent concentration of 1×107 per 100 mL of water. Cysts, such as those represented by Giardia muris or Giardia lamblia, are widespread, disease-inducing, and resistant to most forms of chemical disinfection. A device claiming cyst-removal must show a minimum 3-log reduction (99.9% of cysts removed) from an influent concentration of 1×106 per L or 1×107 per L.
  • It is known to use strong oxidants, such as phenols and hypochlorites, to effectively negate the potential threat of all microorganisms in water; however, these agents must be removed from water before consumption. Known biocompatible antimicrobial agents generally destroy only select microorganisms rather than a broad spectrum of microorganisms, thereby requiring the use of multiple biocompatible antimicrobial agents to effectively negate the potential threat of all microorganisms.
  • One conventional biocompatible antimicrobial agent is known as chlorhexidine. Chlorhexidine is a 1,6-di(4-chlorophenyl-diguanido) hexane having the chemical formula:
  • Figure US20080306301A1-20081211-C00001
  • The IUPAC name for chlorhexidine is N,N″Bis(4-chlorophenyl)-3,12-diimino-2,4,11,13-tetrazatetradecanediimideamide. Chlorhexidine has a high level of antibacterial activity, low mammalian toxicity, and a strong affinity for binding to skin and mucous membranes. It has been used as a topical antiseptic for application to areas such as skin, wounds, and mucous membranes. Chlorhexidine also has been used as a pharmaceutical preservative and as a disinfectant for inanimate surfaces.
  • Historically, chlorhexidine has been used only in its salt soluble forms. Chlorhexidine salts, however, have an extremely bitter taste that must be masked in formulations intended for oral use. In addition, chlorhexidine salts are ineffective for applications requiring insoluble materials.
  • Chlorhexidine's antimicrobial activity is directed mainly toward vegetative gram-positive and gram-negative bacteria. It is ineffective against bacterial spores, except at elevated temperatures. Acid-fast bacilli are merely inhibited and not inactivated by aqueous solutions of chlorhexidine. At relatively low concentrations, chlorhexidine is bacteriostatic, while at higher concentrations, chlorhexidine is rapidly bactericidal. Chlorhexidine's fungicidal activity is subject to species variation. Although chlorhexidine and its known derivatives exhibit some antimicrobial activity, they unfortunately may not be effective against a broad spectrum of microorganism types.
  • Other water soluble antimicrobial chemical agents are known in the art. Representative examples of such conventional materials include soaps/detergents, surfactants, acids, alkalis, heavy metals, halogens, alcohols. phenols, oxidizing agents and alkylating agents. Most of these agents chemically alter (e.g., by an oxidation reaction, etc.) the cellular structure of microbes to inactivate them. These agents may have undesirable side-effects on the affected area of contamination (skin, clothes, paint, etc.) with often deleterious side-effects (discoloration and oxidation).
  • Accordingly, there remains a need for an inexpensive and biocompatible antimicrobial agent that will effectively inactivate a broad spectrum of microorganisms. There is also a need for a practical purification material comprising a biocompatible antimicrobial agent for purifying fluids. Desirably, the purification material would significantly exceed the minimum EPA requirements for designation as a microbial water purifier such that it is suitable for consumer and industry point-of-use applications.
  • SUMMARY OF THE INVENTION
  • A novel antimicrobial compound, purification materials, and methods are provided herein. In a particular embodiment, an antimicrobial material comprises a compound of the formula
  • Figure US20080306301A1-20081211-C00002
  • wherein R1 comprises a straight chained, branched, or cyclic alkyl, alkenyl, alkynyl, or aryl group;
  • wherein R2 and R3, independent of one another, comprise a hydrogen, halogen, hydroxyl, amino, amido, alkylamino, arylamino, alkoxy, aryloxy, nitro, acyl, alkenyl, alkynyl, cyano, sulfo, sulfato, mercapto, imino, sulfonyl, sulfenyl, sulfinyl, sulfamoyl, phosphonyl, phosphinyl, phosphoryl, phosphino, thioester, thioether, anhydride, oximno, hydrazino, carbamyl, phosphonic acid, phosphonato, or a straight, chained, branched, or cyclic alkyl, alkenyl, alkynyl, aryl, heteroaryl, or heterocyclic group; and
  • wherein x and y, independent of one another, are numbers between 1 and 3000.
  • In a particular embodiment, the antimicrobial material comprises chlorhexidine dihydrate, a compound of the formula
  • Figure US20080306301A1-20081211-C00003
  • wherein R1 is methyl, R2 and R3 are chloro-phenyl, x is 6, and y is 1.
  • In another particular embodiment, an antimicrobial material comprises a compound of the formula
  • Figure US20080306301A1-20081211-C00004
  • wherein R4 comprises a straight chained, branched, or cyclic alkyl, alkenyl, alkynyl, or aryl group;
  • wherein R5 and R6, independent of one another, comprise a hydrogen, halogen, hydroxyl, amino, amido, alkylamino, arylamino, alkoxy, aryloxy, nitro, acyl, alkenyl, alkynyl, cyano, sulfo, sulfato, mercapto, imino, sulfonyl, sulfenyl, sulfinyl, sulfamoyl, phosphonyl, phosphinyl, phosphoryl, phosphino, thioester, thioether, anhydride, oximno, hydrazino, carbamyl, phosphonic acid, phosphonato, or a straight chained, branched, or cyclic alkyl, alkenyl, alkynyl, aryl, heteroaryl, or heterocyclic group; and
  • wherein x′ and y′, independent of one another, are numbers between 1 and 3000.
  • In a particular embodiment, the antimicrobial material comprises chlorhexidine base, a compound of the f